The objective of this proposal is to find inhibitors of bradykinin and its congeners that act at the level of their receptors in the lung. The assay proposed for screening candidate compounds is their effect on the binding of labeled iodo-tyrosine-1-kallidin by particulate fractions from lung. Part of the proposed work will be directed toward finding the best tissue preparation and the optimum conditions to reveal that binding of labeled hormone related to the initiation of kinin effects, as opposed to nonspecific or degradative binding. Tissue extracts will be prepared and fractionated by a combination of chromatographic techniques. Each fraction will be tested for its ability to inhibit the binding of labeled kinin by a receptor from lung. In addition, synthetic compounds may be tested in the same system. The compounds or fractions that inhibit binding will then be tested for their ability to inhibit effects of bradykinin on living tissues. Two bioassays are contemplated: guinea pig tracheal rings; and perfused lungs from rabbits, guinea pigs or rats. These bioassays will detect both the inhibitory and toxic effects of the candidate compounds, and their specificity toward kinins. Promising fractions will be characterized chemically, with emphasis on mass spectroscopy.